Cargando…

Inflammation-Related LncRNAs Signature for Prognosis and Immune Response Evaluation in Uterine Corpus Endometrial Carcinoma

BACKGROUNDS: Uterine corpus endometrial carcinoma (UCEC) is one of the greatest threats on the female reproductive system. The aim of this study is to explore the inflammation-related LncRNA (IRLs) signature predicting the clinical outcomes and response of UCEC patients to immunotherapy and chemothe...

Descripción completa

Detalles Bibliográficos
Autores principales: Gu, Hongmei, Song, Jiahang, Chen, Yizhang, Wang, Yichun, Tan, Xiaofang, Zhao, Hongyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201290/
https://www.ncbi.nlm.nih.gov/pubmed/35719911
http://dx.doi.org/10.3389/fonc.2022.923641
_version_ 1784728277577891840
author Gu, Hongmei
Song, Jiahang
Chen, Yizhang
Wang, Yichun
Tan, Xiaofang
Zhao, Hongyu
author_facet Gu, Hongmei
Song, Jiahang
Chen, Yizhang
Wang, Yichun
Tan, Xiaofang
Zhao, Hongyu
author_sort Gu, Hongmei
collection PubMed
description BACKGROUNDS: Uterine corpus endometrial carcinoma (UCEC) is one of the greatest threats on the female reproductive system. The aim of this study is to explore the inflammation-related LncRNA (IRLs) signature predicting the clinical outcomes and response of UCEC patients to immunotherapy and chemotherapy. METHODS: Consensus clustering analysis was employed to determine inflammation-related subtype. Cox regression methods were used to unearth potential prognostic IRLs and set up a risk model. The prognostic value of the prognostic model was calculated by the Kaplan-Meier method, receiver operating characteristic (ROC) curves, and univariate and multivariate analyses. Differential abundance of immune cell infiltration, expression levels of immunomodulators, the status of tumor mutation burden (TMB), the response to immune checkpoint inhibitors (ICIs), drug sensitivity, and functional enrichment in different risk groups were also explored. Finally, we used quantitative real-time PCR (qRT-PCR) to confirm the expression patterns of model IRLs in clinical specimens. RESULTS: All UCEC cases were divided into two clusters (C1 = 454) and (C2 = 57) which had significant differences in prognosis and immune status. Five hub IRLs were selected to develop an IRL prognostic signature (IRLPS) which had value in forecasting the clinical outcome of UCEC patients. Biological processes related to tumor and immune response were screened. Function enrichment algorithm showed tumor signaling pathways (ERBB signaling, TGF-β signaling, and Wnt signaling) were remarkably activated in high-risk group scores. In addition, the high-risk group had a higher infiltration level of M2 macrophages and lower TMB value, suggesting patients with high risk were prone to a immunosuppressive status. Furthermore, we determined several potential molecular drugs for UCEC. CONCLUSION: We successfully identified a novel molecular subtype and inflammation-related prognostic model for UCEC. Our constructed risk signature can be employed to assess the survival of UCEC patients and offer a valuable reference for clinical treatment regimens.
format Online
Article
Text
id pubmed-9201290
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-92012902022-06-17 Inflammation-Related LncRNAs Signature for Prognosis and Immune Response Evaluation in Uterine Corpus Endometrial Carcinoma Gu, Hongmei Song, Jiahang Chen, Yizhang Wang, Yichun Tan, Xiaofang Zhao, Hongyu Front Oncol Oncology BACKGROUNDS: Uterine corpus endometrial carcinoma (UCEC) is one of the greatest threats on the female reproductive system. The aim of this study is to explore the inflammation-related LncRNA (IRLs) signature predicting the clinical outcomes and response of UCEC patients to immunotherapy and chemotherapy. METHODS: Consensus clustering analysis was employed to determine inflammation-related subtype. Cox regression methods were used to unearth potential prognostic IRLs and set up a risk model. The prognostic value of the prognostic model was calculated by the Kaplan-Meier method, receiver operating characteristic (ROC) curves, and univariate and multivariate analyses. Differential abundance of immune cell infiltration, expression levels of immunomodulators, the status of tumor mutation burden (TMB), the response to immune checkpoint inhibitors (ICIs), drug sensitivity, and functional enrichment in different risk groups were also explored. Finally, we used quantitative real-time PCR (qRT-PCR) to confirm the expression patterns of model IRLs in clinical specimens. RESULTS: All UCEC cases were divided into two clusters (C1 = 454) and (C2 = 57) which had significant differences in prognosis and immune status. Five hub IRLs were selected to develop an IRL prognostic signature (IRLPS) which had value in forecasting the clinical outcome of UCEC patients. Biological processes related to tumor and immune response were screened. Function enrichment algorithm showed tumor signaling pathways (ERBB signaling, TGF-β signaling, and Wnt signaling) were remarkably activated in high-risk group scores. In addition, the high-risk group had a higher infiltration level of M2 macrophages and lower TMB value, suggesting patients with high risk were prone to a immunosuppressive status. Furthermore, we determined several potential molecular drugs for UCEC. CONCLUSION: We successfully identified a novel molecular subtype and inflammation-related prognostic model for UCEC. Our constructed risk signature can be employed to assess the survival of UCEC patients and offer a valuable reference for clinical treatment regimens. Frontiers Media S.A. 2022-06-02 /pmc/articles/PMC9201290/ /pubmed/35719911 http://dx.doi.org/10.3389/fonc.2022.923641 Text en Copyright © 2022 Gu, Song, Chen, Wang, Tan and Zhao https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Gu, Hongmei
Song, Jiahang
Chen, Yizhang
Wang, Yichun
Tan, Xiaofang
Zhao, Hongyu
Inflammation-Related LncRNAs Signature for Prognosis and Immune Response Evaluation in Uterine Corpus Endometrial Carcinoma
title Inflammation-Related LncRNAs Signature for Prognosis and Immune Response Evaluation in Uterine Corpus Endometrial Carcinoma
title_full Inflammation-Related LncRNAs Signature for Prognosis and Immune Response Evaluation in Uterine Corpus Endometrial Carcinoma
title_fullStr Inflammation-Related LncRNAs Signature for Prognosis and Immune Response Evaluation in Uterine Corpus Endometrial Carcinoma
title_full_unstemmed Inflammation-Related LncRNAs Signature for Prognosis and Immune Response Evaluation in Uterine Corpus Endometrial Carcinoma
title_short Inflammation-Related LncRNAs Signature for Prognosis and Immune Response Evaluation in Uterine Corpus Endometrial Carcinoma
title_sort inflammation-related lncrnas signature for prognosis and immune response evaluation in uterine corpus endometrial carcinoma
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201290/
https://www.ncbi.nlm.nih.gov/pubmed/35719911
http://dx.doi.org/10.3389/fonc.2022.923641
work_keys_str_mv AT guhongmei inflammationrelatedlncrnassignatureforprognosisandimmuneresponseevaluationinuterinecorpusendometrialcarcinoma
AT songjiahang inflammationrelatedlncrnassignatureforprognosisandimmuneresponseevaluationinuterinecorpusendometrialcarcinoma
AT chenyizhang inflammationrelatedlncrnassignatureforprognosisandimmuneresponseevaluationinuterinecorpusendometrialcarcinoma
AT wangyichun inflammationrelatedlncrnassignatureforprognosisandimmuneresponseevaluationinuterinecorpusendometrialcarcinoma
AT tanxiaofang inflammationrelatedlncrnassignatureforprognosisandimmuneresponseevaluationinuterinecorpusendometrialcarcinoma
AT zhaohongyu inflammationrelatedlncrnassignatureforprognosisandimmuneresponseevaluationinuterinecorpusendometrialcarcinoma